Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarized its active constituents, molecular mechanisms and clinical application for cancer treatment.
Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; drug effects ; Biomedical Research ; methods ; trends ; Brucea ; chemistry ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; pathology ; Phytotherapy

OBJECTIVETo investigate the inducing effect of Brucea javanica on the apoptpsis of HL-60 cells.

METHODHL-60 cells were treated with Brucea javanica 1:100, 1:40, 1:20 (v/v) respectively for 6 h and DNA agarose gel electrophoresis, flow cytometry, fluorescence microscope, electron microscope were used to observe the apoptosis inducing effect of Brucea javanica.

RESULTDNA ladder was seen in the 1:40 group. The apoptosis cell percentages of 1:40 and 1:20 group were 86.8% and 97% respectively. Cells of 1:40 group showed obvious apoptosis character under fluorescence microscope. Cells were induced apoptosis in 1:20 and 1:40 Brucea javanica under electron microscope.

CONCLUSION1:20 and 1:40 Brucea Javanica showed obvious apoptosis inducing effect of HL-60.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Brucea ; chemistry ; HL-60 Cells ; Humans ; Plant Oils ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry

OBJECTIVETo develop an HPLC method for quantitative determination of three quassinoids in Brucea javanic.

METHODThe determination was carried out on a phenomenex C18 column (4.6 mm x 250 mm, 5 microm) with gradient elution program of methol-water at a flow rate of 1.0 mL x min(-1), and the detection wavelength was 270 nm.

RESULTLinearites of bruceine D, brusatol and bruceine H were good (r = 0.9996, 0.9996, and 0.9998) in ranges of 2.52-12.60, 2.19-10.95, and 2.91-14.55 microg, respectively. The average recoveries of bruceine D, brusatol and bruceine H were 100.01%, 100.95% and 100.43% respectively, and RSD of the above three compounds were 0.31% (n = 6), 1.7% ( n = 6) and 1.7% (n = 6), respectively.

CONCLUSIONThe determination results of three batch samples showed that the method was simple, accurate and could be used in the quantitative determination of three components in the B. javanica.

Brucea ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; standards ; Linear Models ; Organic Chemicals ; analysis ; isolation & purification ; standards ; Quality Control

OBJECTIVETo study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice.

METHODSGrowth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot.

RESULTSThe inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05).

CONCLUSIONSIntraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Brucea ; Cell Line, Tumor ; Cisplatin ; Female ; Fruit ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms ; Plant Oils ; pharmacology

Ten compounds were isolated from the stems of Brucea mollis by various chromatographic techniques such as column chromatography on silica gel and Sephadex LH-20, and preparative HPLC, and their structures were elucidated as deacetylated isobrucein B (1), indaquassin X (2), cleomiscosin A (3), cleomiscosin B (4), (+)-lyoniresinol (5), (+)-epipinoresinol(6), (+)-pinoresinol (7), (+)-syringaresinol (8), 4,5-dihydroblumenol A (9) and adenosine (10) on the basis of spectroscopic data analysiS. All compounds were obtained from this plant for the first time, moreover, compound 1 was a new natural product. Compound 2 showed significant cytotoxic activities against the human cell lines HT-29, HepG2, BGC-823 and SKOV3 with IC50 values of 0.84-3.97 micromol x L(-1).
Brucea ; chemistry ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; HT29 Cells ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Plant Extracts ; chemistry ; pharmacology ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

To investigate the effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells.
 Methods: First, A549 cells were divided into a control group and a low, medium or high dose of Brucea javanica oil emulsion groups (0, 2.5, 5.0 or 10.0 mg/mL); then, the cells were divided into a 3-MA+Brucea javanica oil emulsion group and a Brucea javanica oil emulsion group in the presence or absence of 3-methyl adenine (3-MA). Cell counting kit-8 (CCK-8) and clone formation assay were used to detect cell proliferation, while the wound scratch and Transwell assay were used to measure cell migration. Cell immunofluorescence and Western blot were used to analyze autophagy.
 Results: Compared with the control group, the numbers of cell proliferation and colony-formation, the relative cell migration rate and numbers of trans-membrane cells were reduced in a dose-dependent manner in the Brucea javanica oil emulsion groups (all P<0.05). Meanwhile, compared with the control group, the aggregation of microtubule associated protein 1 light chain3 (LC3) green fluorescence and the LC3-II/LC3-I ratios were increased, while p62 level was decreased (all P<0.05) in the high dose group. Compared with the Brucea javanica oil emulsion group (5.0 mg/mL), the cell proliferation, numbers of cell clone formation, cell migration rate and numbers of Transwell transmembrane cells were increased in the 3-MA+Brucea javanica oil emulsion group (all P<0.05).
 Conclusion: Brucea javanica oil emulsion can promote the autophagy of non-small cell lung cancer A549 cells and inhibit the cell proliferation and migration.
A549 Cells ; Autophagy ; drug effects ; Brucea ; chemistry ; Carcinoma, Non-Small-Cell Lung ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Lung Neoplasms ; Plant Oils ; pharmacology

OBJECTIVETo explore the in vitro inhibitive effect and underlying mechanisms of Brucea Javanica oil emulsion (BJOE) on human papilloma virus (HPV) type 16 infected cells.

METHODSThe HPV16 E61E7 immortalized human ectocervical Ect1/E6E7 cell line and the CaSki cell line were selected as the in vitro models of premalignant cervical lesion and cervical cancer respectively. After treated with BJOE at different concentrations (5, 10, 20, and 40 microg/mL) at the operation time points (24, 48, and 72 h), the effects of BJOE on proliferative activities were measured by MTT assay. The morphologic changes of cell apoptosis stained with Hochest 33,258 were observed by fluorescence microscope. The effect on the cell apoptosis rate was analyzed by Annexin V-FITC/PI double-labeled flow cytometry. The mRNA expressions of HPV16 E6 and E7 were determined by semi-quantitative RT-PCR. The protein expressions of HPV16 E6, E7 oncogene, and specifically interacted p53, Rb antioncogene were stained by immunocytochemical staining (Elivison two-step procedure).

RESULTS(1) The proliferative activities of the Ect1/E6E7 cell and the CaSki cell treated with BJOE at different concentrations (5, 10, 20, and 40 p g/mL) at the operation time points (24, 48, and 72 h) were obviously inhibited, showing dose- and time-dependent manners (P <0.05). (2) Typical changes of apoptosis were observed in both HPV 16 positive cell lines after treated with BJOE. The cell apoptosis rates increased markedly after being cultured with BJOE at different concentrations (5, 10, and 20 microg/mL) for 48 h (P < 0.05). (3) After treated with BJOE at different concentrations (5, 10, and 20 microg/mL) for 48 h, the HPV16 E6 and E7 mRNA relative expressions in both HPV 16 positive cell lines decreased significantly (P < 0.05). (4) After treated with BJOE at different concentrations (5, 10, and 20 microg/ mL), the expressions of HPV16 E6, E7, and mutant p53 protein decreased gradually (P < 0.05), while the Rb protein expression increased gradually (P < 0.05).

CONCLUSIONSBJOE showed obvious in vitro inhibitory effects on HPV type 16 infected cells. Its underlying mechanisms might be possibly associated with down-regulating expressions of HPV16 E6 and E7 oncogenes.

Apoptosis ; drug effects ; Brucea ; chemistry ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Female ; Human papillomavirus 16 ; drug effects ; pathogenicity ; Humans ; Oncogene Proteins, Viral ; metabolism ; Papillomavirus E7 Proteins ; metabolism ; Papillomavirus Infections ; Plant Oils ; pharmacology ; Repressor Proteins ; metabolism

Eight compounds were isolated from the stems of Brucea mollis by various chromatographic techniques such as column chromatography on silica gel and Sephadex LH-20, and preparative HPLC, and their structures were elucidated as bruceolline O (1), 1-(1-beta-glucopyranosyl)-1H-indole-3-carbaldehyde (2), canthin-6-one (3), 11-hydroxycanthin-6-one (4), 9-methoxycanthin-6-one (5), 4-methoxycanthin-6-one (6), infractin (7), and beta-carboline-1-propionic acid (8). The cytotoxic activities of compounds 1-8 against HCT-8 and A549 human cell lines were determined, but none of them exhibited significant activity (IC 50 > 10 micromol x L(-1)). Among them, compound 1 is a new indole alkaloid, and compounds 2 and 5-7 were isolated from this plant for the first time.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Brucea ; chemistry ; Carbolines ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Humans ; Indole Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo study the effects of brucea javanica oil on the expression of vascular endothelial growth factor (VEGF) in A549 cell line.

METHODA549 cells were incubated with different concentrations of brucea javanica oil (0.5, 1.25, 2.5, 5 g x L(-1) for 48 h respectively. VEGF level in supernatant was determined by VEGF ELISA kits and mRNA expression of VEGF was evaluated by RT-PCR. PMN in health volunteers was treated as control groups.

RESULTSupernatant VEGF protein and mRNA expression were significantly elevated in A549 cells compared with the mononuclear cells (120.73 vs 21.21, P < 0.05). Brucea javanica oil (2.5 g x L(-1)) could reduced supernatant VEGF protein in A549 cells (20.30 vs 120.73, P < 0.05), but had no effect on the expression of VEGF mRNA (1.0230 vs 0.9573). It was found that brucea javanica oil (5 g x L(-1)) significantly reduced VEGF mRNA expression (0.4682 vs 0.9573, P < 0.05).

CONCLUSIONBrucea javanica oil can depress the VEGF mRNA expression and secretion in A549 cells, which may be one of the mechanisms of its antitumor effect.

Brucea ; chemistry ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation ; drug effects ; Humans ; Plant Oils ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo observe and compare the quality of life (QOL) and survival time in patients with advanced primary hepatic cancer (PHC) after they have been treated by the combination of ganji recipe and interventional therapy with Fructus Bruceae Oil Emulsion (FBE) or by the trans-hepatic arterial chemical embolization (TACE) adopting Seldinger's technique.

METHODSSeventy-seven patients with advanced PHC were randomly assigned to two groups, 37 patients in the control group treated with TACE alone, and 40 in the treatment group with the combined therapy. One therapeutic course was 4 weeks, and the intervention therapy was repeated generally after an interval of 4-6 weeks according to patients'condition ,the average intervention frequency was 2.3 for one case. The QOL and the survival time in patients were evaluated after treatment.

RESULTSSignificant difference was shown in the changes of the Karnofsky score between the two groups (P < 0.05). The scores suggested that the improvements in the treatment group, including patients'physical energy enhancing, symptoms alleviating and overall QOL improving, were superior to those in the control group (P < 0.05). No significant difference of the 3-month survival rate between the two groups was found (P > 0.05), but the 0.5- and 1-year survival rate were significantly superior in the treatment group to those in the control group (67.6% vs. 42.4% and 38.2% vs. 16.1%, respectively). The median survival time in the two groups was 8.9 and 5.3 months respectively.

CONCLUSIONCombination of ganji recipe and interventional therapy with FBE in treating PHC could improve patients' QOL, raise the 0.5- and 1-year survival rate, and prolong the survival time, suggesting TCM treatment has an affirmative significance for enhancing the therapeutic efficacy and improving the prognosis in patients.

Adult ; Aged ; Brucea ; chemistry ; Carcinoma, Hepatocellular ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Embolization, Therapeutic ; methods ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Phytotherapy ; Plant Oils ; administration & dosage ; Quality of Life ; Seeds ; chemistry